Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis
The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/7/312 |
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| author | Lilian Sosa Ana Cristina Calpena Marcelle Silva-Abreu Lupe Carolina Espinoza María Rincón Nuria Bozal Oscar Domenech María José Rodríguez-Lagunas Beatriz Clares |
| author_facet | Lilian Sosa Ana Cristina Calpena Marcelle Silva-Abreu Lupe Carolina Espinoza María Rincón Nuria Bozal Oscar Domenech María José Rodríguez-Lagunas Beatriz Clares |
| author_sort | Lilian Sosa |
| collection | DOAJ |
| description | The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order to provide a local effect. Parameters including internal structure, swelling, porosity, and short-term stability were determined. In addition, drug release profile and ex vivo skin and vaginal permeation studies were carried out. Antifungal efficacy was evaluated against strains of <i>Candida</i> spp. and atomic force microscopy (AFM) supported the results. The tolerance of AmB-gel was studied by evaluating biomechanical properties of skin and determining the irritation level in scarified rabbit skin supported by histological analysis. Results confirmed the development of a thermoreversible AmB-gel with high porosity exhibiting Newtonian behavior at 4 °C and pseudoplasticity at 32 °C as well as optimal stability for at least 90 days. The Amb-gel provided a sustained drug release following a Boltzmann sigmoidal model. Non permeation was observed in skin and vaginal mucosa, showing a high retained amount of AmB of 960.0 and 737.3 µg/g/cm<sup>2</sup>, respectively. In vitro antifungal efficacy showed that AmB-gel was more effective than Free-AmB in inhibiting strains of <i>Candida</i> spp. and these results were corroborated by AFM. Finally, tolerance studies showed that its application did not induce skin irritation nor alter its biophysical properties. Together, these results confirmed that AmB-gel could be proposed as a promising candidate for the clinical status in the treatment of skin and vaginal candidiasis. |
| first_indexed | 2024-04-13T08:00:22Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T08:00:22Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b209d35de1c54f30862afe65646079ee2022-12-22T02:55:17ZengMDPI AGPharmaceutics1999-49232019-07-0111731210.3390/pharmaceutics11070312pharmaceutics11070312Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal CandidiasisLilian Sosa0Ana Cristina Calpena1Marcelle Silva-Abreu2Lupe Carolina Espinoza3María Rincón4Nuria Bozal5Oscar Domenech6María José Rodríguez-Lagunas7Beatriz Clares8Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Biology, Healthcare and the Environment, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainInstitute de Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainThe present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order to provide a local effect. Parameters including internal structure, swelling, porosity, and short-term stability were determined. In addition, drug release profile and ex vivo skin and vaginal permeation studies were carried out. Antifungal efficacy was evaluated against strains of <i>Candida</i> spp. and atomic force microscopy (AFM) supported the results. The tolerance of AmB-gel was studied by evaluating biomechanical properties of skin and determining the irritation level in scarified rabbit skin supported by histological analysis. Results confirmed the development of a thermoreversible AmB-gel with high porosity exhibiting Newtonian behavior at 4 °C and pseudoplasticity at 32 °C as well as optimal stability for at least 90 days. The Amb-gel provided a sustained drug release following a Boltzmann sigmoidal model. Non permeation was observed in skin and vaginal mucosa, showing a high retained amount of AmB of 960.0 and 737.3 µg/g/cm<sup>2</sup>, respectively. In vitro antifungal efficacy showed that AmB-gel was more effective than Free-AmB in inhibiting strains of <i>Candida</i> spp. and these results were corroborated by AFM. Finally, tolerance studies showed that its application did not induce skin irritation nor alter its biophysical properties. Together, these results confirmed that AmB-gel could be proposed as a promising candidate for the clinical status in the treatment of skin and vaginal candidiasis.https://www.mdpi.com/1999-4923/11/7/312thermoreversible gelpoloxamer 407candidiasisamphotericin Bskin and vaginal mucosa |
| spellingShingle | Lilian Sosa Ana Cristina Calpena Marcelle Silva-Abreu Lupe Carolina Espinoza María Rincón Nuria Bozal Oscar Domenech María José Rodríguez-Lagunas Beatriz Clares Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis Pharmaceutics thermoreversible gel poloxamer 407 candidiasis amphotericin B skin and vaginal mucosa |
| title | Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis |
| title_full | Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis |
| title_fullStr | Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis |
| title_full_unstemmed | Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis |
| title_short | Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis |
| title_sort | thermoreversible gel loaded amphotericin b for the treatment of dermal and vaginal candidiasis |
| topic | thermoreversible gel poloxamer 407 candidiasis amphotericin B skin and vaginal mucosa |
| url | https://www.mdpi.com/1999-4923/11/7/312 |
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